Background: Preventing neonates with skin breakdown is a high priority for neonatal care by reviewing clinical guidelines of skin care, implementing new procedures, and updating nurses' knowledge. The study was aimed to evaluate the effect of an educational program about prevention of neonatal skin breakdown on nurses' practices at neonatal intensive care units. Subjects and method: Research design: A quasi-experimental research design was used. Setting: The study was conducted at Neonatal Intensive Care Units (NICUS) of four hospitals (El Salam Hospital, Al Hayat Hospital, Specialized Maternity Hospital, and EL-Nasr Specialized Hospital) which are affiliated to the Universal Health Insurance Authority (UHIA) of Port Said governorate. Subjects: Convenience sampling included all nurses (70) working at the aforementioned hospitals, as well as 50 neonates in each program phase (150) who admitted during the time of data collection. Tools used for data collection: first, an observational checklist and second, scale termed as the Neonatal Skin Condition Score (NSCS). Results: statistically significant differences were found between nurses' total practice levels pre & immediate post, pre & follow up phase (p ≤ 0.005). Also, between the immediate post and follow-up phase of program implementation (p ≤ 0.001). Conclusion: implementing an educational program significantly improved nurses' practices and decreased neonatal skin breakdown. Recommendations: Providing continuous training education programs for nurses about prevention of skin breakdown in NICU.